HIV蛋白酶中突变的有序积累赋予对利托那韦的耐药性。

Ordered accumulation of mutations in HIV protease confers resistance to ritonavir.

作者信息

Molla A, Korneyeva M, Gao Q, Vasavanonda S, Schipper P J, Mo H M, Markowitz M, Chernyavskiy T, Niu P, Lyons N, Hsu A, Granneman G R, Ho D D, Boucher C A, Leonard J M, Norbeck D W, Kempf D J

机构信息

Department of Anti-Infective Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA.

出版信息

Nat Med. 1996 Jul;2(7):760-6. doi: 10.1038/nm0796-760.

DOI:10.1038/nm0796-760

PMID:8673921

Abstract

Analysis of the HIV protease gene from the plasma of HIV-infected patients revealed substitutions at nine different codons selected in response to monotherapy with the protease inhibitor ritonavir. Mutants at valine-82, although insufficient to confer resistance, appeared first in most patients. Significant phenotypic resistance required multiple mutations in HIV protease, which emerged subsequently in an ordered, stepwise fashion. The appearance of resistance mutations was delayed in patients with higher plasma levels of ritonavir. Early mutants retained susceptibility to structurally diverse protease inhibitors, suggesting that dual protease inhibitor therapy might increase the duration of viral suppression.

摘要

对HIV感染患者血浆中的HIV蛋白酶基因进行分析发现，在针对蛋白酶抑制剂利托那韦单药治疗而选择的9个不同密码子处发生了替换。缬氨酸82位点的突变体虽然不足以产生耐药性，但在大多数患者中最早出现。HIV蛋白酶中的多个突变导致了显著的表型耐药性，这些突变随后以有序、逐步的方式出现。利托那韦血浆水平较高的患者中，耐药突变的出现有所延迟。早期突变体对结构多样的蛋白酶抑制剂仍保持敏感性，这表明双重蛋白酶抑制剂疗法可能会延长病毒抑制的持续时间。